The long-term objective of this proposal is to develop a more thorough understanding of hematopoiesis in molluscs, especially schistosome-transmitting snails. Specifically, the following problems will be addressed: (1) factors controlling normal production of hemocytes in the schistosome-transmitting snail, Biomphalaria glabrata; (2) the source and chemical nature of the mitogenic stimuli following infection of B. glabrata by larval trematodes; (3) biochemical stages of development of B. glabrata hemocytes during hematopoiesis; and (4) the role of the hematopoietic tissue in snail schistosome compatibility. This research may lead to a better understanding of the molluscan internal defense (immune) system, which directly determines the capacity of B. glabrata to serve as a disease vector. Furthermore, this project may result in an invertebrate model for the study of cell proliferation. With the use of autoradiographic, histological, and ultrastructural techniques, the effect of snail age, circadian rhythms, as well as the duration of the cell cycle and its component phases, will be investigated. In addition, an in vitro system for studying hematopoiesis will be developed. Next, homogenates of schistosome and echinostome larval trematodes will be injected into B. glabrata, and mitogenic fractions will be isolated and partly characterized. Also, effects of mechanical trauma and hemocyte depletion will be studied. Hemocyte ontogeny will be investigated at the ultrastructural level, with the use of enzyme cytochemistry and lectin probes. Finally, the role of the hematopoietic tissue in susceptibility to schistosome infection will be studied in B. glabrata in which hematopoiesis has been either suppressed (by Delta-irradiation or colchicine) or stimulated (by trematode-associated mitogens). In addition, transplantation of hematopoietic tissue from resistant to susceptible snails will be employed.